Scorpion venom eases sting of brain tumors

August 4, 2006

A new method of delivering a dose of radioactive iodine -- using a manufactured version of scorpion venom as a carrier -- targets gliomas without affecting neighboring tissue or body organs. A phase I clinical trial conducted in 18 patients showed the approach to be safe, and a larger phase II trial is under way to assess the effectiveness of multiple doses.

A new method of delivering a dose of radioactive iodine - using a manufactured version of scorpion venom as a carrier - targets gliomas without affecting neighboring tissue or body organs. A phase I clinical trial conducted in 18 patients showed the approach to be safe, and a larger phase II trial is under way to assess the effectiveness of multiple doses.

Dr. Adam N. Mamelak, a neurosurgeon at Cedars-Sinai Medical Center in Los Angeles, led the phase I trial and is first author of an article in the August Journal of Clinical Oncology.

The key ingredient is TM-601, a synthetic version of a peptide, or protein particle, that naturally occurs in the venom of the giant yellow Israeli scorpion. TM-601 binds to glioma cells and has an unusual ability to pass through the blood-brain barrier.

"We're using the TM-601 primarily as a carrier to transport radioactive iodine to glioma cells, although data suggest that it may also slow down the growth of tumor cells. If studies continue to confirm this, we may be able to use it in conjunction with other treatments, such as chemotherapy, because there may be a synergistic effect. TM-601's ability to impede cancer growth could allow us to reduce the dose of chemotherapy to achieve a therapeutic effect," said Mamelak, codirector of the Pituitary Center at Cedars-Sinai.

About 17,000 U.S. residents are diagnosed with gliomas each year. The tumors are extremely aggressive and deadly, with only 8% of patients surviving two years and 3% surviving five years from time of diagnosis.

Patients who consented to participate in the phase I study first underwent tumor removal surgery. Fourteen to 28 days later, a single, low dose of radioactive iodine (I-131) attached to TM-601 was injected through a small tube into the cavity from which the tumor had been removed.

Although TM-601 had been tested in earlier laboratory and animal experiments, it had never been given to humans. The primary objective of this study was to document that I-131/TM-601 could be administered to humans safely. The researchers sought to begin to assess the drug's antitumor effect and dosing standards. Six patients agreed to receive additional doses at one of three different levels (0.25 mg of TM-601, 0.5 mg of TM-601, and 1 mg of TM-601), each carrying the same amount of iodine.

"In this first human trial, treatment of patients with recurrent high-grade glioma with a single intracavitary dose of I-131/TM-601 was well tolerated to the maximum dose. ... Very few adverse side effects occurred during the initial 22-day observation period, suggesting the dosing level of peptide used in this study is safe and well-tolerated in humans," the article said.

While median length of survival for all patients was 27 weeks, two patients, both women in their early 40s, had a "complete radiographic response," meaning there was no evidence of residual tumor, according to MRI. These patients were still alive beyond 33 and 35 months after surgery, despite the low dose of TM-601 and radiation levels below expected therapeutic thresholds.

Analyses also showed that most of the radioactivity delivered by the drug left the region within 24 hours of administration. That which lingered was "tightly localized to the tumor cavity and surrounding regions, suggesting discrete binding to the tumor."

The drug was eliminated primarily through the urine, with radiation doses to the thyroid and other vital organs remaining extremely low.

Mamelak said TM-601 binds to tumors other than gliomas, and this therapy will be studied in a variety of tumor types. He conducted this study with colleagues from City of Hope Cancer Center in Duarte, CA, the University of Alabama at Birmingham, St. Louis University in Missouri, and TransMolecular of Birmingham, which also provided funding.

For more information from the Diagnostic Imaging archives:

Imaging offers insight into blood-brain barrier permeability

MR diffusion maps track response to tumor therapy

Intraoperative high-field MR guides neurosurgery

MRS differentiates pediatric tumors in pons